Micro-rna biomarkers and methods of using same

Abstract

A procedure and an apparatus are described for identifying individuals at risk of pulmonary tumour and/or for diagnosing a pulmonary tumour using the study of levels of expression of miRNA in the blood or another biological fluid. Also described are a method and a compound for reducing or eliminating a risk of pulmonary tumour by rebalancing the miRNAs that are underexpressed or overexpressed.

1 . A method comprising:
 determining the level of expression of at least two miRNA from the miRNA listed in Tables Ia, Ic, IIa, IIc, Va, Vc, VIa, or VIc in a biological sample from a subject, and   comparing the level of expression of said miRNA from said sample from said subject to the level of expression of said miRNA from a control biological sample.   
     
     
         2 . The method of  claim 1 , comprising determining the level of expression of at least six miRNA from the miRNA listed in Tables Ia, Ic, IIa, IIc, Va, Vc, VIa, or VIc. 
     
     
         3 . A method comprising:
 determining the level of expression of at least two miRNA listed in Table Ib or Id in a biological sample from a subject, and   comparing the level of expression of said miRNA from said sample from said subject to the level of expression of said miRNA from a control biological sample,   wherein a change or deviation in the level of expression of said at least two miRNA in said biological sample from said control biological sample identifies a subject at risk of manifesting a tumor.   
     
     
         4 . The method of  claim 3 , comprising determining the level of expression of at least six miRNA listed in Table Ib or Id. 
     
     
         5 . The method of  claim 3 , wherein said miRNA are the miRNA listed in Table Ie. 
     
     
         6 . A method comprising:
 determining the level of expression of at least two miRNA listed in Table IIb or IId in a biological sample from a subject, and   comparing the level of expression of said miRNA from said sample from said subject to the level of expression of said miRNA from a control biological sample,   wherein a change or deviation in the level of expression of said at least two miRNA in said biological sample from said control biological sample identifies a subject at risk of manifesting an aggressive tumor.   
     
     
         7 . The method of  claim 6 , comprising determining the level of expression of the six miRNA listed in Table Ib or IId. 
     
     
         8 . The method of  claim 6 , wherein said miRNA are the miRNA listed in Table IIe, IIf or IIg. 
     
     
         9 .- 14 . (canceled) 
     
     
         15 . The method of  claim 1 , further comprising
 calculating a plurality of real quotients by determining a ratio between the level of expression of at least one pair of miRNA from at least two miRNA listed in Tables Ia, Ic, IIa, IIc, Va, Vc, VIa, or VIc;   comparing each of the real quotients with a respective control value; and   determining the real quotients which deviate from the respective control quotient value.   
     
     
         16 . The method of  claim 15 , comprising determining a ratio between the level of expression of at least one pair of miRNA from at least six miRNA listed in Tables Ia, Ic, IIa, IIc, Va, Vc, VIa, or VIc. 
     
     
         17 . The method of  claim 15 , wherein said miRNA are the miRNA listed in Tables Ie, IIe, IIf, IIg, Ve, Vf, VIe or VIf. 
     
     
         18 . The method of  claim 15 , further comprising determining a number or percentage of real quotients which deviate from the respective control value. 
     
     
         19 . The method of  claim 15 , wherein for each of the calculated quotients a respective control quotient is associated, represented by a ratio of the levels of expression for the miRNA in a control biological sample relative to a biological sample of a same type. 
     
     
         20 . The method of  claim 15 , wherein calculating the plurality of real quotients comprises using the expression level of at least two miRNA from the miRNA listed in Tables Ia, Ic, IIa, IIc, Va, Vc, VIa, or VIc. 
     
     
         21 . The method of  claim 15 , wherein calculating the plurality of real quotients comprises determining a predetermined number or a predetermined percentage of quotients from among the levels of expression, wherein the quotients are selected from at least one of the quotients as listed in Tables IIIa, IIIc, IVa, IVc, VIIa, VIIc, VIIIa, or VIIIc. 
     
     
         22 . The method of  claim 21 , wherein the quotients are selected from at least six of the quotients as listed in Tables IIIa, IIIc, IVa, IVc, VIIa, VIIc, VIIIa, or VIIIc. 
     
     
         23 .- 43 . (canceled)